BackgroundEnrollment in time-sensitive endovascular stroke trials can be challenging because of an inability to consent a debilitated patient. Often the legally authorized representative is not on site. Remote consent procedures in the US are inconsistent with the majority of sites shunning these approaches. The current pandemic with visitor restrictions highlights the need for enhancing these options.MethodsRemote electronic and phone consent procedures specifically for endovascular stroke trials from two comprehensive stroke centers (CSC) are presented. An overview of the genesis of informed consent procedures in the US is also included.ResultsThe two CSCs identified as Institution-1 and Institution-2 are large tertiary systems. Institution-1 is a non-profit university-affiliated academic medical center in rural geography. Institution-2 is an HCA hospital in an urban environment. Both serve patients through a spoke-and-hub network, have participated in multiple randomized endovascular stroke trials, and have successfully used these remote options for enrollment. A tiered approach is employed at both institutions with an emphasis on obtaining informed consent in person and resorting to alternatives methods when efforts to that are unsuccessful. A rationale for electronic and phone consent is included, followed by step-by-step illustration of the process at each institution.ConclusionTwo examples of remote electronic or phone consent procedures from institutions in different geographic environments and organization structures demonstrate that these options can be successfully used for enrollment in stroke trials. The current pandemic highlights the need to enhance these approaches while maintaining appropriate adherence to ethical and legal frameworks.
The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research was created in 1974. The Commission’s charge was to develop guidelines for human subject research based on ethical principles that would underpin such research. The output of the Commission after in-depth discussions over the next 4 years was the Belmont Report, which was published in the Federal Register in April 1979.1 Three core ethical principles identified by the Belmont Report were respect for persons, beneficence, and justice. The guidance for obtaining legally effective informed consent provided by the US Department of Health and Human Services code of federal regulations (CFR) Title 45 (Public Welfare), Part 46 (Protection of Human Subjects) – “45 CFR part 46” is grounded in the Belmont Report’s first principle of “respect for persons”. (https://www.ecfr.gov/cgibin/retrieveECFR?gp=&SID=83cd09e1c0f5c6937cd9d7513160fc3f&pitd=20180719&n=pt45.1.46&r=PART&ty=HTML).
Since then, obtaining appropriate informed consent from the patient or next of kin is a key ethical and medicolegal requirement – and in the US it is the right of any patient prior to undergoing an invasive procedure.2 The informed consent obtained from the subject or the subject’s legally authorized representative (LAR) is a process that needs to be followed not only in letter but in spirit. The food and drug administration (FDA) final rule regarding exception to informed consent in emergency medical research was published in 19963 and contains explicit criteria governing conditions in which critically ill patients can have access to potentially lifesaving (but unproven) therapies. This has been recently updated to include new guidance on obtaining electronic informed consent.4 Approval of remote or electronic informed consent protocols or exception for informed consent is determined by the local institutional review boards (IRB) and is dependent on their comfort and level of understanding vis a vis informed consent procedures especially in an emergency setting.5
Acute ischemic stroke secondary to large vessel occlusion constitutes a medical emergency requiring prompt intervention to reperfuse the brain. These interventions are now evidence-based and constitute standard of care. Further progress is dependent on continuous research and clinical trials. Large vessel stroke patients represent a unique group debilitated by their neurological deficits and often unable to comprehend their state or surroundings. Transferred by emergency medical services and often from nursing homes or independent senior living facilities these patients are not in immediate touch with their families. Obtaining a face-to-face informed consent from a next of kin for enrollment in a clinical trial highly dependent on time to treatment is often not possible and thus these patients are excluded from enrollment. This may lead to prolongation of the trial and also introduces a certain bias by enrolling only those patients whose relatives are readily available and potentially have a stronger family structure which may impact outcomes.6
The current COVID-19 pandemic with restricted limited visitor policy in most institutions is particularly an environment that may benefit from evolution in consent procedures for now and for the future. This brief article describes the remote consent procedure adopted at two institutions involved in endovascular trials for acute ischemic stroke. The article also presents a review of literature and remote consenting methods adopted in other clinical trials.
We describe remote consent processes for endovascular stroke trials at two institutions. These are large comprehensive stroke centers that have participated in multiple acute ischemic stroke trials. The process at both these institutions was developed to allow for enrollment of eligible patients without causing any delay in treatment.
The first institution is a university affiliated tertiary referral comprehensive stroke center covering a large rural geography with a relatively low population density. Often a stroke patient arrives or is transferred much ahead of the family and next of kin, limiting the capacity to do in-person informed consent. The remote consent process was initially developed several years ago to improve enrollment in the stroke trials and since then has been a part of the protocol for all endovascular stroke trials. The same pathway will be adopted in the current COVID environment and beyond the acute pandemic when families may not be allowed to accompany a patient. The rationale for the proposal to the IRB was based on the following key points:
The following tiered methodology was approved by the IRB and successfully used to enroll patients in whom face-to-face consent from the next of kin could not be obtained.
Similar to the first one, the second institution is also a large comprehensive stroke center but contrary to the first one it is an HCA hospital in an urban environment. The institution is the prime referral base for a large geography and population. The institution developed a remote consent protocol for an ongoing endovascular stroke trial specifically to allow enrollment during the COVID-19 pandemic. The rationale was similar to that described for the previous institution. The tiered remote consent process in case face-to-face consent cannot be obtained is described below:
The article describes remote consent processes adopted for use in two centers for emergent endovascular stroke trials. The critical requirement for obtaining remote consent is to balance adherence to core ethical principles with the capacity to enroll neurologically debilitated patients who may not be able to consent themselves. Endovascular stroke therapy is a standard of care for large vessels strokes, future trials may assess different treatment options for recanalization or may access subgroups for whom this therapy is not of proven efficacy. These groups can include large vessel stroke patients with a higher core infarct on imaging, second order cerebrovascular occlusions, or large vessels strokes with relatively minor neurological deficits.
Physician phone elicitation of consent in the field has been shown to be feasible and effective in increasing enrollment, especially for time-sensitive trials such as acute ischemic stroke.7 The EXTEND-IA8 allowed the option of verbal phone consent from a LAR if in-person consent could not be obtained and the ESCAPE9 trial allowed for waiver or deferral of consent when necessary and where possible according to local IRB approval. The use of a smartphone platform for obtaining electronic informed consent was demonstrated by Haussen et al for enrollment in the DAWN10 trial with a follow-up study showing overall acceptable response of the electronic process by the consenters.11 The FAST-MAG trial implemented a novel voice over the internet phone system and simultaneous activation of multiple physicians to connect the first available investigator with on-scene first responders and patient or their legally authorized representative.12 By facilitating and expediting the informed consent procedure using voice-over-internet phone, the trial was able to enroll a substantial number of patients in the first hour after stroke symptom onset.12 13 Patient comprehension of informed consent has been shown to be non-inferior to face-to-face consent in emergency medicine trials.14
Technological progress over the past decade has transformed communications. Widespread availability of smart phones, tablets, faster networks, and targeted applications are allowing physicians to remotely communicate with their patients and even conduct a virtual clinic visit. The current COVID-19 pandemic has highlighted these modes of communication with an emphasis on telemedicine to cope with the lack of in-person interactions.15 16 Further enhancement of these approaches may require an update of the health informatics infrastructure17 and a renewed evaluation of these possibilities by IRBs.
This article illustrates two examples for remote electronic or phone consent procedures adopted by comprehensive stroke centers to sustain enrollment in emergent endovascular stroke trials. This is particularly pertinent during the COVID-19 pandemic where many hospitals do not allow visitors or severely limit the ability of LAR or LAR admittance into the hospital. There are other examples in the literature on how these processes can be developed, keeping in mind the federal guidance for informed consent, the ethical principles at stake, and the unique settings of a clinical trial. The onus of balancing these criteria is on the sponsor, the principal investigators, and on the local IRB. The current pandemic has presented an opportunity to evaluate and enhance electronic communication tools and update the rules of conducting ethical clinical research in compliance with the code of federal regulations.